The UA_handle: a versatile submotif in stable RNA architectures†

Abstract

Stable RNAs are modular and hierarchical 3D architectures taking advantage of recurrent structural motifs to form extensive non-covalent tertiary interactions. Sequence and atomic structure analysis has revealed a novel submotif involving a minimal set of five nucleotides, termed the UA_handle motif (5′XU/ANnX3′). It consists of a U:A Watson–Crick: Hoogsteen trans base pair stacked over a classic Watson–Crick base pair, and a bulge of one or more nucleotides that can act as a handle for making different types of long-range interactions. This motif is one of the most versatile building blocks identified in stable RNAs. It enters into the composition of numerous recurrent motifs of greater structural complexity such as the T-loop, the 11-nt receptor, the UAA/GAN and the G-ribo motifs. Several structural principles pertaining to RNA motifs are derived from our analysis. A limited set of basic submotifs can account for the formation of most structural motifs uncovered in ribosomal and stable RNAs. Structural motifs can act as structural scaffoldings and be functionally and topologically equivalent despite sequence and structural differences. The sequence network resulting from the structural relationships shared by these RNA motifs can be used as a proto-language for assisting prediction and rational design of RNA tertiary structures.

Determination of riboswitch structures: Light at the end of the tunnel?

“…43 Recently, a thorough analysis has aimed to surmise more intimate tertiary interactions and the arrangement of structural elements in the FMN riboswitch. 44 The X-ray structure of the FMN riboswitch 13 agrees with several conclusions from this theoretical study and, remarkably, confirms the global similarity between the large T-loop-based architectural modules of the riboswitch and 23S rRNA, designated as T-loop-PK domains. 44 Interestingly, the study failed to predict an A-minor-like tertiary contact because of the replacement of an adenine, found in A-minor motifs, by a conserved guanine.…”

“…44 The X-ray structure of the FMN riboswitch 13 agrees with several conclusions from this theoretical study and, remarkably, confirms the global similarity between the large T-loop-based architectural modules of the riboswitch and 23S rRNA, designated as T-loop-PK domains. 44 Interestingly, the study failed to predict an A-minor-like tertiary contact because of the replacement of an adenine, found in A-minor motifs, by a conserved guanine. Such a substitution apparently weakens the tertiary contact and may be functionally important for the alternative pairing of the switching sequence in the absence of ligand.…”

Tertiary architecture of theOceanobacillus iheyensisgroup II intron

“…T-loops are distinctive because they commonly contain a gap that is filled by intercalation of an adenine from an adjacent strand (A245) (Krasilnikov and Mondragon 2003), rather than an adenine from the same strand at the fourth loop position, as is typical for GNRA loops. Indeed, the DI T-loop is perfectly superimposable with the structure of the ATP binding aptamer (Dieckmann et al 1996;Jaeger et al 2009), where AMP is bound at the same position as the intercalated base A245 (Fig. 4B).…”

The tedious task of finding homologous noncoding RNA genes

“…For large RNAs, in particular ribosomal RNAs, structures are still most reliably derived using the ''phylogenetic method,'' that is, by investigating covariations of homologous sequence positions. Covariations beyond the helical regions provide insights into tertiary interactions and allow the discovery of aggregate motifs , such as K-turns (Klein et al 2001) or UA-handles (Jaeger et al 2009), which are functionally important hallmarks of many RNA families.…”